Virus Diseases Commons^™

Host Cell Responses To Zika Virus Infection, Bikash Ranjan Sahoo

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV) in 2015 as a significant human pathogen causing neurological diseases in infants as well as adults is a serious global health concern. A clear understanding of the mechanisms involved in ZIKV replication in infected host cells as well as the host responses to virus infection are keys to the development of therapeutic strategies against ZIKV. Studies conducted in this dissertation demonstrate that ZIKV infection induces the activation of mTOR signaling cascade that promotes viral protein accumulation and infectious progeny production. While both mTORC1 and mTORC2 are essential for ZIKV replication, the observation that depletion …

Euadb: A Resource For Covid-19 Test Development And Comparison, Alyssa Woronik, Henry W. Shaffer, Karin Kiontke, Jon M. Laurent, Ronald Zambrano, Mariah Daley, Jef D. Boeke, David H. Fitch

Biology Faculty Publications

Due to the sheer number of COVID-19 (coronavirus disease 2019) cases there is a need for increased world-wide SARS-CoV-2 testing capability that is both efficient and effective. Having open and easy access to detailed information about these tests, their sensitivity, the types of samples they use, etc. would be highly useful to ensure their reproducibility, to help clients compare and decide which tests would be best suited for their applications, and to avoid costs of reinventing similar or identical tests. Additionally, this resource would provide a means of comparing the many innovative diagnostic tools that are currently being developed in …

Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential …

General Public Perception Of Social Media, Impact Of Covid-19 Pandemic, And Related Misconceptions, Rabiya Ali, Shireen Jawed, Mukhtiar Baig, Ahmed Azam Malik, Fatima Syed, Rehana Rehman

Department of Biological & Biomedical Sciences

Objectives: To investigate the general public perception of social media (SM), impact of COVID-19 (SARS-CoV-2) pandemic, and related misconceptions among Pakistani population.
Methodology: Cross-sectional study conducted during the peak of COVID-19 in Pakistan between May-June 2020 comprised of 2307 Pakistani male and female participants. Subjects under 18 years of age and nationality other than Pakistani were excluded. An online questionnaire was administered via the Internet using various kinds of social media.
Results: The study comprised of 2307 male and female participants; 2074(89.90%) were using SM for seeking COVID-19 information, 450 (20%) were using both Facebook (FB) and WhatsApp (WA) and …

Human Apobec3 Variations And Viral Infection, Shiva Sadeghpour, Saeideh Khodaee, Mostafa Rahnama, Hamzeh Rahimi, Diako Ebrahimi

Plant Pathology Faculty Publications

Human APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) enzymes are capable of inhibiting a wide range of endogenous and exogenous viruses using deaminase and deaminase-independent mechanisms. These enzymes are essential components of our innate immune system, as evidenced by (a) their strong positive selection and expansion in primates, (b) the evolution of viral counter-defense mechanisms, such as proteasomal degradation mediated by HIV Vif, and (c) hypermutation and inactivation of a large number of integrated HIV-1 proviruses. Numerous APOBEC3 single nucleotide polymorphisms, haplotypes, and splice variants have been identified in humans. Several of these variants have been reported to be associated …

Blue Biotechnology: Computational Screening Of Sarcophyton Cembranoid Diterpenes For Sars-Cov-2 Main Protease Inhibition, Mahmoud A A. Ibrahim, Alaa H M. Abdelrahman, Mohamed A M. Atia, Tarik A. Mohamed, Mahmoud F. Moustafa, Abdulrahim R. Hakami, Shaden A M. Khalifa, Fahad A. Alhumaydhi, Faris Alrumaihi, Syed Hani Abidi

Department of Biological & Biomedical Sciences

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the …

Nanomaterial-Based Biosensors For Detection Of Salmonella Typhimurium And Avian Influenza Virus H5n1 In Poultry, Xinge Xi

Graduate Theses and Dissertations

This research focused on developing biosensing method and biosensing device for rapid detection of pathogens in poultry: Salmonella Typhimurium and avian influenza virus H5N1. The first part of the dissertation reports an original research on the development of a portable biosensing device for Salmonella detection. The device was designed and constructed based on a previously developed optical biosensing method, using immuno-magnetic nanoparticles to specifically capture target bacteria, and immuno-quantum dot beads to label the target bacteria for fluorescence detection. All the actions of sample mixing, magnetic separation, and fluorescence detection were controlled automatically in a disposable microfluidic chip in the …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Multi-Subunit Sars-Cov-2 Vaccine Design Using Evolutionarily Conserved T- And B- Cell Epitopes, Burkitkan Akbay, Syed Hani Abidi, Mahmoud A A. Ibrahim, Zhussipbek Mukhatayev, Syed Ali

Department of Biological & Biomedical Sciences

The SARS-CoV-2 pandemic has created a public health crisis worldwide. Although vaccines against the virus are efficiently being rolled out, they are proving to be ineffective against certain emerging SARS-CoV-2 variants. The high degree of sequence similarity between SARS-CoV-2 and other human coronaviruses (HCoV) presents the opportunity for designing vaccines that may offer protection against SARS-CoV-2 and its emerging variants, with cross-protection against other HCoVs. In this study, we performed bioinformatics analyses to identify T and B cell epitopes originating from spike, membrane, nucleocapsid, and envelope protein sequences found to be evolutionarily conserved among seven major HCoVs. Evolutionary conservation of …

Effect Of Clinical Isolate Or Cleavage Site Mutations In The Sars-Cov-2 Spike Protein On Protein Stability, Cleavage, And Cell-Cell Fusion, Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, Carole L. Moncman, Rachel Thompson, Jean M. Branttie, Kerri Beth Boggs, Cheng-Yu Wu, Daisy W. Leung, Rebecca E. Dutch

Molecular and Cellular Biochemistry Faculty Publications

The trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2-infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. A furin cleavage site at the border between the S1 and S2 subunits (S1/S2) has …

Assessment Of Pathogenic Changes In The Gut-Liver Axis In Plwh With Heavy Alcohol Drinking And Gut Dysbiosis Marked By Decreased Butyrogenic Potential., Smita Ghare, Vaughn Bryant, Richa Singhal, Sabina Gautam, Chanakya Charan Tirumala, Andrea Reyes-Vega, Craig J. Mcclain, Ronald Cohen, Varand Govind, Robert L. Cook, Shirish Barve

Faculty and Staff Scholarship

Purpose: People living with HIV infection (PLWH) experience increasing risk for non-AIDS diseases including liver dysfunction and injury. Both HIV-infection and heavy alcohol drinking (HAD) are known to cause gut microbial dysbiosis and systemic inflammation that may potentially contribute to altered Gut-Liver axis. However, the specific pathogenic features associated with combinatorial harmful effects of alcohol and HIV infection on gut-liver interactions are not completely understood. This study evaluate the pathogenic changes in the Gut-Liver axis in PLWH with HAD.

Rebuilding Trust On Routine Immunization In Era Of Covid-19 Fear-Role That Civil Society Organizations Can Play Hands-In-Hand With Immunization Program, Ameer Muhammad, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq

Medical College Documents

No abstract provided.

Predictors Of Mortality In Hospitalized Covid-19 Patients: A Mexican Population-Based Cohort Study., Fernando Mesta Dr., Ángel Mario Coll Dr., Miguel Ángel Ramírez M.Sc., Livan Delgado-Roche Dr.

BioMedicine

Objectives. COVID-19 outbreak brings a challenge to healthcare systems. The sex, age, and cardiometabolic comorbidities have been considered risk factors for disease severity. To evaluate the association between risk factors with death as well the risk of death in hospitalized COVID-19 patients.

Methods. The present cross-sectional cohort study, includes hospitalized SARS‑CoV‑2 confirmed cases. Data analysis was performed using the National COVID‑19 Cases Report Database. Pearson´s χ² test and odds ratios (95% CI) were calculated to determine the association between variables. Thereafter, risk of death was evaluated by Cox proportional hazards model.

Results. A total of 67 …

Scaling Up Information Sharing On Hiv-Associated Neurocognitive Disorder: Raising Awareness And Knowledge Among Key Stakeholders, Renato M. Liboro, Paul A. Shuper, Lori E. Ross

Psychology Faculty Research

Although the majority of specialists and researchers in the field of HIV/AIDS are aware and knowledgeable about HIV-associated neurocognitive disorder (HAND) as a condition that affects as much as 50% of people living with HIV/AIDS (PLWH), research has documented that many health care and service providers who work directly with PLWH are either unaware of HAND or believe they do not know enough information about HAND to effectively support their clients experiencing neurocognitive challenges. Based on the findings of a qualitative study that interviewed 33 health care and service providers in HIV/AIDS services to identify and examine their awareness and …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Neurocognitive Impairment In People Living With Human Immunodeficiency Virus (Hiv): Risk Factors And Mortality, Zaeema Naveed

Theses & Dissertations

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH) with clinical and public health implications. Studies have generated inconsistent results regarding etiological factors for NCI in PLWH and a brief user-friendly predictive tool is desirable in clinical practice to assess the probability of having NCI in PLWH. Furthermore, factors associated with clinically meaningful decline in neurocognitive status and survival disadvantage for patients with NCI are understudied in the post-cART era. The goal of this dissertation was to investigate factors associated with baseline NCI and neurocognitive decline and the association …

Mathematical Models Of Covid-19, Kate Faria

Honors Program Theses and Projects

For more than a year, the COVID-19 pandemic has been a major public health issue, affecting the lives of most people around the world. With both people’s health and the economy at great risks, governments rushed to control the spread of the virus. Containment measures were heavily enforced worldwide until a vaccine was developed and distributed. Although researchers today know more about the characteristics of the virus, a lot of work still needs to be done in order to completely remove the disease from the population. However, this is true for most of the infectious diseases in existence, including Influenza, …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

S.O.S. For Covid-19 (Subjective And Objective Screening): Are Asymptomatic Cases Truly Without Warning Signs?, Nathan Hughes

Honors College Theses

This study investigates the usefulness of five objective signs, evaluates relationships between objective signs with symptoms of COVID-19, and assesses the accuracy of ambient forehead temperature with tympanic temperature. Data were collected at Wayne State University. Blood oxygen levels and blood pressure were measured via pulse oximeters and blood pressure cuff. Body temperature was measured with a thermometer via the temple and the forehead. Smell was tested with two scented markers. None of the 29 participants confirmed a positive COVID-19 test. Therefore, only relationships between vital sign measurements were reported. No significant correlations were revealed upon analysis. Infrared and temporal …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Nih Funding For Vaccine Readiness Before The Covid-19 Pandemic, Anthony E. Kiszewski, Ekaterina Galkina Cleary, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Rapid development of vaccines for COVID-19 has relied on the application of existing vaccine technologies. This work examines the maturity of ten technologies employed in candidate vaccines (as of July 2020) and NIH funding for published research on these technologies from 2000–2019. These technologies vary from established platforms, which have been used successfully in approved products, to emerging technologies with no prior clinical validation. A robust body of published research on vaccine technologies was supported by 16,358 fiscal years of NIH funding totaling $17.2 billion from 2000–2019. During this period, NIH funding for published vaccine research against specific pandemic threats …

Evaluation Of Serum Ferritin For Prediction Of Severity And Mortality In Covid-19- A Cross Sectional Study, Sibtain Ahmed, Zeeshan Ansar Ahmed, Imran Siddiqui, Naveed Haroon Rashid, Maheen Mansoor, Lena Jafri

Department of Pathology and Laboratory Medicine

Background: Ferritin even though widely recognized as a representative of total body iron stores, its prognostic utility is linked with COVID-19. This study was aimed at evaluation of the association of ferritin with severity in Coronavirus disease 2019 (COVID-19), hospitalized patients and to test the hypothesis that it is an independent predictor of mortality.
Material and methods: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University (AKU), Karachi. Medical records of all in-patients including both genders, and all age groups with documented COVID-19 from 1st March to 10^th August 2020 were reviewed. …

Environmentally Marginalized Populations: The "Perfect Storm" For Infectious Disease Pandemics, Including Covid-19, Gabriella Y. Meltzer, Oyemwenosa Avenbuan, Christina Awada, Oluwakemi B. Oyetade, Tricia Blackman, Simona Kwon Drph, Mph, Esther Erdei Phd, Judith T. Zelikoff Phd

Journal of Health Disparities Research and Practice

COVID-19 has exacted a severe toll on the United States population’s physical and mental health and its effects have been felt most severely among people of color and low socioeconomic status. Using illustrative case studies, this commentary argues that in addition to COVID-19 health disparities created by psychosocial stressors such as the inability to socially distance and access quality healthcare, environmental justice communities have the additional burden of disproportionate exposure to toxic contaminants that contribute to their higher risk of COVID-19. Environmental contaminants including heavy metals and persistent organic pollutants found contaminating their nearby environments can alter the immune response, …

Long-Term Dynamics Of The Kidney Disease Epidemic Among Hiv-Infected Individuals, Heather Gudaz, Henry A. Ogu, Elissa J. Schwartz

Spora: A Journal of Biomathematics

One of many risks facing HIV+ individuals is the development of kidney dysfunction and end stage kidney disease (ESKD). A differential equation-based mathematical model was developed to assess the impact of antiretroviral therapy on the progression to kidney disease and on reducing mortality due to kidney failure. Analytical and numerical predictions of long-term HIV+ ESKD prevalence show that therapy can lead to either extremely low levels of disease prevalence or increased prevalence, depending on drug efficacy levels and mechanisms of action. Maintenance of HIV+ ESKD prevalence below one individual is possible with sufficient efficacy (e.g., 99%) against the progression from …

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …

An Innovation In Flipped Class Room: A Teaching Model To Facilitate Synchronous And Asynchronous Learning During A Pandemic, Rehana Rehman, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Objective: To conduct an on line Flipped Class Room (FCR) to facilitate synchronous (in class activity) and asynchronous learning [Virtual Learning Environment (VLE)] and acquire feedback of the learning experience from medical students at Aga Khan University.
Methods: This interventional study was conducted with year II students undergoing Endocrine Reproduction Module at the Aga Khan University during April 13 to May 22, 2020. Pre reading material and pretest was shared with the students via Virtual Learning Environment (VLE) one week before the class. Microsoft Teams was used to conduct online session by two facilitators, where student discussion on case studies …

Use Of Lymesim 2.0 To Assess The Potential For Single And Integrated Management Methods To Control Blacklegged Ticks (Ixodes Scapularis; Acari: Ixodidae) And Transmission Of Lyme Disease Spirochetes, Shravani Chitineni, Elizabeth R. Gleim, Holly D. Gaff

Undergraduate Honors Theses

Annual Lyme disease cases continue to rise in the U.S. making it the most reported vector-borne illness in the country. The pathogen (Borrelia burgdorferi) and primary vector (Ixodes scapularis; blacklegged tick) dynamics of Lyme disease are complicated by the multitude of vertebrate hosts and varying environmental factors, making models an ideal tool for exploring disease dynamics in a time- and cost-effective way. In the current study, LYMESIM 2.0, a mechanistic model, was used to explore the effectiveness of three commonly used tick control methods: habitat-targeted acaricide (spraying), rodent-targeted acaricide (bait boxes), and white-tailed deer targeted acaricide (4-poster …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …

Impact Of Covid-19 On Ohio's National Parks Visitation, Ryan Grzeschik

Williams Honors College, Honors Research Projects

The COVID-19 pandemic has fundamentally changed the way in which society operates in order to get the novel disease under control. Businesses throughout the United States have had to close or reduce provided services, stay at home orders have secluded many people, and social distancing limits contact between others so many are turning to the parks system to cope with these changes. This study aims to find how the visitation of national parks in Ohio have been affected through the first six months of the pandemic. Visitation statistics were compared from March to August of 2020 to those same months …